Nailfold videocapillaroscopy and serum vascular endothelial growth factor in probable COVID-19-induced chilblains: a cross-sectional study to assess microvascular impairment
Authors: Yora Mostmans, Vanessa Smith, Maurizio Cutolo, Karin Melsens, Salomé Battist, Asma Benslimane, Francis Corazza, Bertrand Richert, Olivier Michel, Athanassios Kolivras
Journal: British Journal of Dermatology (2022)

Nailfold videocapillaroscopy and serum VEGF in probable COVID-19-induced chilblains: a cross-sectional study to assess microvascular impairmentDear Editor, Coronavirus disease 2019 (COVID-19)-induced chilblains represent a type I interferon (IFN) induced microangiopathy (1) .The objective of this cross-sectional study is to identify whether microangiopathic changes can be detected biologically through the serum levels of vascular endothelial growth factor (VEGF) and clinically through nailfold videocapillaroscopy (NVC).Between April and July 2020, we investigated serum VEGF levels in 17 patients presenting with probable COVID-19-induced chilblains at the dermatology department of Centre Hospitalier Universitaire Saint-Pierre (Brussels), and 8 healthy controls (HC) by an enzyme-linked immunosorbent essay (ELISA) (VEGF Quantikine Bio-Techne).Inclusion criteria were: (a) presence of chilblain-like lesions during COVID-19 pandemic; (b) no history of chilblains; (c) no exposure to cold before onset of chilblains; (d) persistence of lesions >48 hours; (e) clinical and histopathological confirmation of chilblains; (f) no history of lupus erythematosus, systemic sclerosis, photosensitive eruption, or any other dermatosis within the affected area; (g) antinuclear antibodies (ANA) ≤1:160 without specific identification.All HC subjects were included before COVID-19 pandemic (2018-2019).NVC was performed on 14 patients.All fingers except thumbs, were assessed with a X200-magnification contact lens (Optilia Mediscope, Sweden).Quantitative parameters were compared with 14 age/sex-matched HC, using the capillaroscopic protocol from the EULAR SG MCRD (2) .Table 1 shows demographic data of the included patients and explorative analysis of quantitative NVC parameters.Statistical analysis was performed by StatView version 5.0.Nonparametric tests were used to determine P-value, Mann-Whitney U test for continuous variables (p<0.05).Kendall's rank correlation was used to test the relationship between variables.Patients with chilblains had significantly decreased capillary density (p<0.001) and increased number of capillary dilations (p<0.05),abnormal capillary shapes (p<0.05) and microhaemorrhages (p<0.02) on NVC compared to HC.There was a positive correlation between age and capillary density for both HC and chilblain patients (p<0.05).While no significant differences in VEGF levels were seen between patients and HC, VEGF levels in patients with chilblains showed significant positive correlation with age, capillary density and presence of normally shaped capillaries and significant negative correlation with irregularly dilated capillaries, plexus visibility score and percentage dilated capillaries/total capillaries.This is the first study on probable COVID-19-induced chilblains where microangiopathic changes, clinically detected on NVC, are correlated biologically with serum levels of VEGF, a known biomarker for vascular homeostasis.Our results show that chilblain patients had significantly decreased capillary density and significantly increased number of capillary dilations, abnormal capillary shapes and microhaemorrhages on NVC compared to HC.These findings confirm that reliable NVC signs of microvasculopathy in probable COVID-19-induced chilblains can be identified.This is only the second NVC study providing evidence of microvasculopathy in probable COVID-19-induced chilblains (3) .There is also limited NVC research in more severe COVID-19 manifestations, such as confirmed COVID-19 pneumonia (4) or Multisystem Inflammatory Syndrome in Children (MIS-C), showing signs of systemic microangiopathy in these patients (5) .VEGF serum levels were determined in 17/18 chilblain patients and showed no significant differences compared to HC.This absence of significant difference could be consistent with the known less severe disease course (6) .In our study VEGF levels in chilblain patients positively correlated significantly with age and capillary density.Significant negative correlation was seen with irregularly dilated capillaries.These findings suggest that VEGF could be a reliable marker for capillary density and (irregular) capillary dilation in COVID-19 chilblain patients.Also, in these patients, age could be a protective factor for loss of